Methylamine → HCID 22050796, compound

HRID 1832088Notes

Reaction equation

HRID 1832088 reaction equation
[Br:1][C:2]1[C:3](=[O:29])[N:4]([C:19]2[CH:20]=[C:21]([CH:25]=[CH:26][C:27]=2[F:28])[C:22](O)=[O:23])[C:5]([CH3:18])=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17].ClC(OCC(C)C)=O.[CH3:38][N:39]1CCOC[CH2:40]1.CN>CN(C)C=O>[Br:1][C:2]1[C:3](=[O:29])[N:4]([C:19]2[CH:20]=[C:21]([CH:25]=[CH:26][C:27]=2[F:28])[C:22]([N:39]([CH3:40])[CH3:38])=[O:23])[C:5]([CH3:18])=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17]

Participants

6

Reactant 4

HCID 6329MethylamineHCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 22050518HCID 22050518, compound

Product 1

HCID 22050796HCID 22050796, compoundYield 30%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 3-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl]-4-fluorobenzoic acid (1 g, 2.1 mmol) in N,N-dimethylformamide (20 mL) was cooled to −10 C. Isobutyl chloroformate (0.27 mL, 2.1 mmol) and N-methyl morpholine (0.23 mL, 2.1 mmol) were added to the reaction vessel. After stirring at −10 C for 20 minutes, a solution of N-methyl amine (2.1 mL, 4.2 mmol, 2 M in THF) was added and the reaction mixture was warmed to room temperature as it stirred for 18 hours. The reaction mixture was concentrated in vacuo and partitioned between water and ethyl acetate. The organic layer was washed with brine and concentrated in vacuo. The solid was chromatographed on silica (95:5 methylene chloride : isopropyl alcohol) to give the desired product as a white powder (0.31 g, 30%). 1H NMR (400 MHz, CD3OD) δ 7.64 (m, 1H), 7.50 (dd, J=2.4 and 7.2 Hz, 1H), 7.45 (t, J=9.6 Hz, 1H), 7.04 (t, J=9.2 Hz, 2H), 6.65 (s, 1H), 5.36 (s, 2H), 3.09 (s, 3H), 3.05 (s, 3H), 2.10 (s, 3H) ppm. 19F NMR (400 MHz, CD3OD) δ−111.51 (1 F), −115.88 (1 F), −121.90 (1 F) ppm. ES-HRMS m/z 495.0508 (M+H calcd for C22H19BrF3N2O3 requires 495.0526).

Workup

  1. stirringstirred for 18 hours
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. custompartitioned between water and ethyl acetate
  4. washThe organic layer was washed with brine
  5. concentrationconcentrated in vacuo
  6. customThe solid was chromatographed on silica (95:5 methylene chloride : isopropyl alcohol)

Sources & evidence

ORD record
ord-c8c32d282db1462a8aa113d3ffe07244
Source dataset
uspto-grants-2006_06
Patent number
US07067540B2

Reaction notes

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